Regenerative Decline

Written by David M Gardiner

Embryonic regeneration and regenerative decline has been most extensively studied in the frog, Xenopus laevis. Early stage (pre-differentiation) limb buds of Xenopus can regenerate perfectly. As a larva progresses through metamorphic climax, regenerative ability declines as differentiation progresses. The sequence of differentiation in the developing limb is from proximal to distal and from posterior to anterior, and the loss of regenerative ability occurs in the same sequence. Proximal amputation prior to the onset of differentiation leads to a fully formed regenerate. At later stages when proximal levels no longer regenerate, distal levels are still undifferentiated, and are still able to regenerate. At even later stages, regeneration from distal amputations becomes imperfect, and ultimately regenerative ability is lost entirely. The progressive loss of regenerative ability is an intrinsic property of the limb cells, and not a consequence of hormonal or other systemic changes in the animal. A young limb bud grafted to an older animal can still regenerate, even though the host animal’s limbs cannot. Conversely an older limb bud grafted to a younger, regeneration-competent host is not induced to regenerate. This intrinsic loss of regenerative ability in Xenopus is associated with a progressive loss of the ability to reactivate expression of genes involved in growth and pattern formation.